Pirfenidone Capsules

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Pirfenidone Capsules contain NLT 95.0% and NMT 105.0% of the labeled amount of pirfenidone (C₁₂H₁₁NO).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The UV spectrum of the pirfenidone peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: Dissolve 1.4 mL of triethylamine in each liter of water.Adjust with phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile, methanol, and Buffer (22:13:65)

Standard solution: 0.1 mg/mL of USP Pirfenidone RS in Mobile phase

Sample stock solution: Nominally 1.1 mg/mL of pirfenidone in Mobile phase prepared as follows. Transfer a portion of contents from Capsules (NLT 10), equivalent to 267 mg of pirfenidone, to a 250-mL volumetric flask. Add 150 mL of Mobile phase, and shake on a mechanical shaker for 10 min. Sonicate for 10 min and cool to ambient temperature. Dilute with Mobile phase to volume.

Sample solution: Nominally 0.11 mg/mL of pirfenidone from the Sample stock solution in Mobile phase. Pass a portion of the solution through a suitable filter of 0.45-μm pore size, and discard the initial 2–3 mL of filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

Column: 4.6-mm × 25-cm; 5-μm packing L7

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 15 μL

Run time: NLT 1.5 times the retention time of pirfenidone

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of pirfenidone (C₁₂H₁₁NO) in the portion of Capsules taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of pirfenidone from the Sample solution

r_S = peak response of pirfenidone from the Standard solution

C_S = concentration of USP Pirfenidone RS in the Standard solution (mg/mL)

C_U = nominal concentration of pirfenidone in the Sample solution (mg/mL)

Acceptance criteria: 95.0%–105.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

4.1 Tier 1

Medium: Water; 1000 mL

Apparatus 2: 50 rpm, with a suitable sinker

Time: 30 min

Standard solution: 0.134 mg/mL of USP Pirfenidone RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size and discard the first 3 mL of filtrate.

Transfer 5.0 mL of the filtrate to a 10-mL volumetric flask and dilute with Medium to volume.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 318 nm

Path length: 2.0 mm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of pirfenidone (C₁₂H₁₁NO) dissolved:

Result = (A_U/A_S) × C_S × V × D × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Pirfenidone RS in the Standard solution (mg/mL)

V = volume of Medium, 1000 mL

D = dilution factor, 2

L = label claim (mg/Capsule)

Tolerances: NLT 85% (Q) of the labeled amount of pirfenidone (C₁₂H₁₁NO) is dissolved

4.2 Tier 2

Medium: pH 7.0 phosphate buffer containing 1750 units of pancreatin/L, 1000 mL, deaerated

Apparatus 2: 50 rpm, with a suitable sinker

Time: 30 min

Standard solution: 0.134 mg/mL of USP Pirfenidone RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size and discard the first 3 mL of filtrate.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 318 nm

Path length: 1.0 mm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of pirfenidone (C₁₂H₁₁NO) dissolved:

Result = (A_U/A_S) × C_S × V × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Pirfenidone RS in the Standard solution (mg/mL)

V = volume of Medium, 1000 mL

L = label claim (mg/Capsule)

Tolerances: NLT 85% (Q) of the labeled amount of pirfenidone (C H NO) is dissolved

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Buffer, Sample stock solution, and Sample solution: Prepare as directed in the Assay.

Solution A: Acetonitrile, methanol, and Buffer (22:13:65)

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.10 μg/mL each of USP Pirfenidone Related Compound A RS and USP Pirfenidone Related Compound B RS in Solution A

Standard solution: 0.15 μg/mL of USP Pirfenidone RS in Solution A

Sensitivity solution: 0.05 μg/mL of USP Pirfenidone RS from the Standard solution in Solution A

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; 5-μm packing L7

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 50 μL

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[Note - The relative retention times in Table 2 are provided as information that could aid in peak assignment.]

Table 2

Suitability requirements

Resolution: NLT 6.0 between pirfenidone related compound A and pirfenidone related compound B, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any specified or unspeci

ed degradation product in the portion of Capsules taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any specified or unspecified degradation product from the Sample solution

r_S = peak response of pirfenidone from the Standard solution

C_S = concentration of USP Pirfenidone RS in the Standard solution (mg/mL)

C_U = nominal concentration of pirfenidone in the Sample solution (mg/mL)

Acceptance criteria: The reporting threshold is 0.05%.

Any unspecified degradation product: NMT 0.10%

Total degradation products: NMT 0.3%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Pirfenidone RS

USP Pirfenidone Related Compound A RS

5-Methylpyridin-2-amine.

C₆H₈N₂ 108.14

USP Pirfenidone Related Compound B RS

5-Methylpyridin-2(1H)-one.

C₆H₇NO 109.13